ChemComm
Communication
We acknowledge the support of the National Science Founda-
tion, grant CHE 0717702. AMG and JCL thank the Ministerio de
´
Ciencia e Innovacion and Comunidad de Madrid grants CTQ2009-
10343, CTQ2012-32114 and S2009/PPQ-1752, respectively. A
patent has been issued for the work described in this paper.
Notes and references
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1 See for example. C. Avendano and J. C. Menendez, Medicinal
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2 T. B. Johnson and G. E. Hilbert, Science, 1929, 69, 579–580;
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3 W. Koenigs and E. Knorr, Chem. Ber., 1901, 34, 957–981.
4 B. Helferich and E. Schmitz-Hillebrecht, Chem. Ber., 1933, 66, 378–383.
5 H. Vorbruggen and P. Strehlke, Chem. Ber., 1973, 106, 3039–3061;
U. Niedballa and H. Vorbruggen, Angew. Chem., Int. Ed. Engl., 1970,
9, 461–462; U. Niedballa and H. Vorbruggen, J. Org. Chem., 1974, 39,
3654–3660.
Scheme 3 NPOE donors with free C30–OH in nucleoside assembly.
6 H. Vorbruggen and C. Ruh-Pohlenz, Handbook of Nucleoside Synthesis,
John Wiley Sons, Inc., New York, 2001.
7 S. Knapp and W. C. Sieh, Tetrahedron Lett., 1992, 33, 827–880;
S. Hanessian, G. Huang, C. Chenel, R. Machaalani and
O. Loiseleur, J. Org. Chem., 2005, 70, 6721–6734; S. I. Hashimoto,
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10 Q. Zhang, J. Sun, Y. Zhu, F. Zhang and B. Yu, Angew. Chem., Int. Ed.,
2011, 50, 4933–4936.
Scheme 4 C20 differentiated ribo-glycosyl donors.
11 H. L. Frush and H. S. Isbell, J. Res. Natl. Bur. Stand., 1941, 27,
413–428.
12 B. Capon and S. P. McManus, Neighboring Group Participation,
Plenum Press, New York, 1976.
´
13 B. Fraser-Reid and J. C. Lopez, Top. Curr. Chem., 2011, 301, 1–31.
14 H. Paulsen, Angew. Chem., Int. Ed. Engl., 1982, 21, 155–173.
15 For examples see ref. 6, Table 1.
16 C. V. S. Ramamurty, P. Ganney, C. S. Rao and B. Fraser-Reid, J. Org.
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17 M. Mach, U. Schlueter, F. Mathew, B. Fraser-Reid and K. C. Hazen,
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Scheme 5 Xylo-NPOE precursors for ribo-glycosyl donors and thence to differ-
ent 30-substituted ribonucleosides.
19 General experimental procedure for N-glycosylation. To a stirred
solution of the NPOE (1.0 mmol) in anhydrous CH3CN (1 mL) was
added a solution of silylated nucleobase (1.2 mmol) in CH3CN
(2 mL) and allowed to stir at 0 1C for 10 min. To this was added a
solution of NIS (1.1 mmol) and Yb(OTf)3 (30 mol%) in CH3CN (2 mL)
at 0 1C and the mixture was allowed to stir at room temperature for
the appropriate time (B3–10 h, analysis by TLC). After which, the
reaction mixture was quenched with saturated Na2S2O3 (5 mL) and
extracted with CH2Cl2 (3 ꢁ 10 mL). The combined extracts were
dried over anhydrous Na2SO4 and concentrated in vacuum. The
resulting crude mixture was purified by column chromatography on
silica gel to afford the pure nucleoside.
The Reverse Strategy facilitates syntheses of such fraudulent
nucleosides as shown in Scheme 5. Thus, the xylofuranose NPOE
27a, (readily available from xylose the least expensive furanose
sugar),16 gave differentiated 27c smoothly. As exemplified with
azide, a single inversion leads to C30 substituted ribofuranosyl
donors such as 28. We then divided the latter into several
portions, each of which was used to glycosylate a different
nucleobase so as to obtain an assortment of nucleosides differing
only at the aglycon. One of the products so obtained was the 20 B. Fraser-Reid, J. Lu, K. N. Jayaprakash and J. C. Lopez, Tetrahedron:
30-azido 30-deoxy-ribonucleoside 29.
´
Asymmetry, 2006, 17, 2449–2463; J. C. Lopez, A. Agocs, C. Uriel,
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A. M. Gomez and B. Fraser-Reid, Chem. Commun., 2005, 5088–5090;
J. C. Lopez, J. Ventura, C. Uriel, A. M. Gomez and B. Fraser-Reid, Org.
Lett., 2009, 11, 4128–4131.
In summary, we have shown that readily-prepared strategi-
cally functionalized n-pentenyl orthoesters (NPOEs) can be
coupled to nucleobases efficiently at temperatures as low as
ꢀ78 1C, such that functional groups at C50, C30 and C20 are
´
´
21 C. A. A. van Boeckel and T. Beets, Tetrahedron Lett., 1983, 24,
3775–3778; S. Sogabe, H. Ando, M. Koetsu and H. Ishihara, Tetra-
hedron Lett., 2006, 47, 6603–6607.
tolerated, as is a free C30–OH. This Reverse Strategy therefore 22 J. J. K. Novak and F. Sorm, Collect. Czech. Chem. Commun., 1962, 27,
902–905; J. Skoda, I. Bartosek and F. Sorm, Collect. Czech. Chem.
permits prior extensive structural modifications to the ribose
sub-unit, and late installation of the nucleobase, confident of
Commun., 1962, 27, 906–907.
23 Nucleosides and nucleotides as antitumor and antiviral agents, ed.
b-D orientation. Convergent assembly is therefore optimized.
C. K. Chu and D. C. Baker, Plenum Press, New York, 1993.
c
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